ZDHHC19 is a zinc finger palmitoyltransferase that catalyzes S-palmitoylation, a post-translational modification essential for protein membrane targeting and cellular signaling 1. The enzyme localizes to the endoplasmic reticulum, Golgi apparatus, and plasma membrane where it regulates diverse cellular processes 2. ZDHHC19 palmitoylates key proteins including p62/SQSTM1 to enhance autophagosome recruitment and selective autophagy 1, and STAT3 to promote dimerization and transcriptional activation 3. In spermatogenesis, ZDHHC19 forms a stable complex with TEX38 at the plasma membrane of spermatids, where it palmitoylates ARRDC5 and is essential for normal sperm head morphogenesis 24. ZDHHC19 knockout male mice are sterile due to abnormal sperm morphology and reduced motility 4. The enzyme has significant disease relevance, being frequently amplified in human cancers including 39% of lung squamous cell carcinomas, where it promotes tumorigenesis through STAT3 activation 3. ZDHHC19 is also upregulated in sepsis and correlates with poor prognosis 5, and accelerates osteosarcoma progression via the Wnt/β-catenin pathway 6. These findings establish ZDHHC19 as a critical regulator of autophagy, reproduction, and cancer progression.